Zhang He, Huang Jun-Jie, Wang Jing, Hu Mi, Chen Xia-Chao, Sun Wei, Ren Ke-Feng, Ji Jian
MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China.
Department of Polymer Science and Engineering, Faculty of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, Zhejiang, China.
ACS Biomater Sci Eng. 2019 Dec 9;5(12):6610-6616. doi: 10.1021/acsbiomaterials.9b01353. Epub 2019 Nov 12.
Surface-mediated gene delivery appears to be potential gene delivery modes for various applications. Still, controlled and smart delivery manners are required especially considering the need for gene therapy to deliver gene with selectivity. A surface that can effectively payload DNA, promote cell adhesion, and stimuli response is an important prerequisite. Here, we report a matrix metalloproteinase (MMP)-responsive surface-mediated gene delivery system by combining MMP-degradable hydrogel with a breath figure (BF) porous film. The MMP-degradable hydrogel containing plasmid DNA was loaded into the surface pores of the BF film as DNA reservoirs. The upper surface without hydrogel on the BF film served as footholds of integrin adhesions. MMP is one of the important endogenous signals in tumor-related pathologic changes, and MMP expressions in cancer cells are significantly higher than those in normal cells. Consequently, our surface-mediated gene delivery locally and rapidly released the payload DNA in response to cancer cells and transfected them. This work highlights the importance of the combination of stimuli-response and surface-mediated gene delivery to functional materials, showing good potential applications in the field of gene therapy.
表面介导的基因传递似乎是适用于各种应用的潜在基因传递方式。然而，尤其是考虑到基因治疗需要选择性地传递基因，仍需要可控且智能的传递方式。一个能够有效负载DNA、促进细胞黏附并具有刺激响应性的表面是一个重要的先决条件。在此，我们通过将基质金属蛋白酶（MMP）可降解水凝胶与呼吸图案（BF）多孔膜相结合，报道了一种MMP响应性表面介导的基因传递系统。将含有质粒DNA的MMP可降解水凝胶作为DNA储存库加载到BF膜的表面孔中。BF膜上没有水凝胶的上表面作为整合素黏附的立足点。MMP是肿瘤相关病理变化中的重要内源性信号之一，癌细胞中的MMP表达明显高于正常细胞。因此，我们的表面介导基因传递能够响应癌细胞并局部快速释放负载的DNA，进而对其进行转染。这项工作突出了刺激响应与表面介导基因传递相结合应用于功能材料的重要性，在基因治疗领域显示出良好的潜在应用前景。
